Human apyrase represents a highly promising therapy for treatment of acute myocardial infarction. This enzyme strongly inhibits platelet activation and aggregation with modest bleeding risk. Using a protein informatics approach, we have successfully engineered human apyrases which exhibit both antiplatelet and anti-inflammatory activities. With the Phase I grant support, we will determine whether optimized human apyrases, in combination with tPA, induce rapid and sustained coronary artery recanalization without increasing bleeding risk. PUBLIC HEALTH RELEVANCE: We will utilize a coronary thrombotic model in dogs to validate whether human apyrase more effectively improve coronary patency than clopidogrel without increasing bleeding risk.